title: Safety and immunogenicity of the HPV-16/18 AS04-adjuvanted vaccine in HIV-positive women in South Africa: a partially-blind randomised placebo-controlled study.
abstract: In developing countries, risk of human papillomavirus (HPV) infection may be increased by the high prevalence of human immunodeficiency virus (HIV) infection. We evaluated the safety and immunogenicity of the HPV-16/18 AS04-adjuvanted vaccine in HIV-infected women in South Africa. Asymptomatic HIV-positive women aged 18-25 years (N=120) were stratified by CD4⁺ T-cell count and randomised (1:1) to receive HPV-16/18 vaccine (Cervarix®; GlaxoSmithKline Vaccines) or placebo (Al[OH]3) at 0, 1 and 6 months (double-blind). HIV-negative women (N=30) received HPV-16/18 vaccine (open label). Anti-HPV-16/18 antibody and CD4⁺ T-cell responses, CD4⁺ T-cell count, HIV viral load, HIV clinical stage and safety were evaluated for 12 months. The safety and reactogenicity profile of the HPV-16/18 vaccine was comparable in HIV-positive and HIV-negative women. Irrespective of baseline HPV status, all HIV-positive and HIV-negative women who received the HPV-16/18 vaccine were seropositive for both HPV-16 and HPV-18 after the second vaccine dose (month 2) and remained seropositive for both antigens at month 12. Anti-HPV-16/18 antibody titres at month 12 remained substantially above levels associated with natural infection. The HPV-16/18 vaccine induced sustained anti-HPV-16/18 CD4⁺ T-cell responses in both HIV-positive and HIV-negative women. No impact of baseline CD4⁺ T-cell count or HIV viral load was observed on the magnitude of the immune response in HIV-positive women. In HIV-positive women, CD4⁺ T-cell count, HIV viral load and HIV clinical stage were unaffected by HPV-16/18 vaccine administration. In conclusion, the HPV-16/18 AS04-adjuvanted vaccine appears immunogenic and well-tolerated in women with HIV infection. Study ID: 107863/NCT00586339.
authors.affiliation: Department of Obstetrics and Gynaecology, Groote Schuur Hospital/University of Cape Town, Cape Town, South Africa; Institute of Infectious Diseases and Molecular Medicine, University of Cape Town, Cape Town, South Africa. Electronic address: lynette.denny@uct.ac.za.
authors.forename: Lynette
authors.initials: L
authors.lastname: Denny
authors.forename: Bronwyn
authors.initials: B
authors.lastname: Hendricks
authors.forename: Chivaugn
authors.initials: C
authors.lastname: Gordon
authors.forename: Florence
authors.initials: F
authors.lastname: Thomas
authors.forename: Marjan
authors.initials: M
authors.lastname: Hezareh
authors.forename: Kurt
authors.initials: K
authors.lastname: Dobbelaere
authors.forename: Christelle
authors.initials: C
authors.lastname: Durand
authors.forename: Caroline
authors.initials: C
authors.lastname: Hervé
authors.forename: Dominique
authors.initials: D
authors.lastname: Descamps
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage*; D000293:Adolescent; D000328:Adult; D000536:Aluminum Hydroxide / Q000008:administration & dosage*; D000914:Antibodies, Viral / Q000097:blood; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D064420:Drug-Related Side Effects and Adverse Reactions / Q000453:epidemiology / Q000473:pathology; D005260:Female; D006678:HIV / Q000302:isolation & purification; D015658:HIV Infections / Q000150:complications / Q000276:immunology*; D052162:Human papillomavirus 16 / Q000276:immunology; D052161:Human papillomavirus 18 / Q000276:immunology; D006801:Humans; D008050:Lipid A / Q000008:administration & dosage / Q000031:analogs & derivatives*; D030361:Papillomavirus Infections / Q000276:immunology / Q000517:prevention & control* / Q000821:virology; D053918:Papillomavirus Vaccines / Q000008:administration & dosage / Q000009:adverse effects* / Q000276:immunology*; D016037:Single-Blind Method; D013019:South Africa; D014611:Vaccination / Q000009:adverse effects / Q000379:methods; D019562:Viral Load; D055815:Young Adult
chemical_list: C532963:ASO4 mixture; D000276:Adjuvants, Immunologic; D000914:Antibodies, Viral; D008050:Lipid A; D053918:Papillomavirus Vaccines; C510352:human papillomavirus vaccine, L1 type 16, 18; D000536:Aluminum Hydroxide
keywords: APC; ART; ATP; BARC; Bio Analytical Research Corporation; CI; ELISA; GMT; HIV; HPV; HPV vaccination; HPV-16/18 AS04-adjuvanted vaccine; Human immunodeficiency virus (HIV); Human papillomavirus (HPV); IDMC; Immunogenicity; Independent Data Monitoring Committee; MPL; NOCD; PMTCT; Preventing Mother-to-Child Transmission of HIV; SAE; Safety; TVC; WHO; World Health Organisation; according-to-protocol; antigen-presenting cell; antiretroviral therapy; confidence interval; enzyme-linked immunosorbent assay; geometric mean antibody titre; human immunodeficiency virus; human papillomavirus; monophosphoryl lipid A; new-onset chronic disease; serious adverse event; total vaccinated cohort